Cellular uptake, antitumor response and tumor penetration of cisplatin-loaded milk protein nanoparticles

Abstract

The casein nanoparticles cross-linked by transglutaminase were prepared, and cisplatin (CDDP), as a model antitumor drug, was loaded into the casein nanoparticles. These nanoparticles were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and zeta potential. The uptake and penetration of nanoparticles in 2- and 3-dimensional SH-SY5Y cells were examined at 37 °C and 4 °C. The in vivo biodistribution of the nanoparticles was investigated using near-infrared fluorescence (NIRF) imaging and ion-coupled plasma mass spectrometry (ICP-MS). The antitumor effect of CDDP-loaded nanoparticles was evaluated on hepatic H22 tumor-bearing mice model via intravenous administration. It is found that the obtained nanoparticles showed spherical shape with the size of 257 nm, and drug loading content of 10%. These CDDP-loaded casein nanoparticles have the extraordinary capabilities to penetrate cell membrane barriers, target tumor and inhibit tumor growth. The tumor growth inhibition of CDDP-loaded nanoparticles is 1.5-fold higher than that of free CDDP. Further, the penetration examination of the CDDP-loaded casein nanoparticles in the tumor tissue demonstrated that the nanoparticles had the ability to penetrate the tumor and deliver CDDP to the tumor more deeply and affect the cells far from the vasculature.